Evolutionarily conserved antigens in autoimmune disease: implications for an infective aetiology.
The immune system has evolved to eliminate or inactivate infectious organisms. An inappropriate response against self-components (autoantigens) can result in autoimmune disease. Here we examine the hypothesis that some evolutionarily conserved proteins, present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates autoimmune disease in susceptible individuals. We focus on seven autoantigens, of which at least four, glutamate decarboxylase, pyruvate dehydrogenase, histidyl-tRNA synthetase and alpha enolase, have orthologs in bacteria. Citrullinated alpha-enolase, a target for autoantibodies in 40% of patients with rheumatoid arthritis, is our main example. The major epitope is highly conserved, with over 90% identity to human in some bacteria. We propose that this reactivity of autoantibodies to shared sequences provides a model of autoimmunity in rheumatoid arthritis, which may well extend to other autoimmune disease in humans.
Wegner
Natalia
N
Kennedy Institute of Rheumatology Division, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK.
Wait
Robin
R
Venables
Patrick J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001419:Bacteria / Q000235:genetics / Q000276:immunology; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D018716:Molecular Mimicry; D008969:Molecular Sequence Data
D000942:Antigens, Bacterial; D001324:Autoantigens; D016056:Immunodominant Epitopes